Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study

Invest New Drugs. 2013 Oct;31(5):1283-93. doi: 10.1007/s10637-013-9962-7. Epub 2013 Apr 27.


Purpose: Some targeted anticancer agents are associated with serious ventricular tachyarrhythmias, which may be predicted by electrocardiographic evaluation of drug-related QT prolongation. We studied the effects of nintedanib (BIBF 1120; an oral, triple angiokinase inhibitor targeting vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors) on the QT interval in patients with renal cell carcinoma (RCC) participating in an open-label phase II trial.

Methods: Treatment-naïve, adult patients with unresectable/metastatic, clear cell RCC received nintedanib 200 mg twice daily. QT intervals were evaluated at baseline (day -1), on day 1 (after the first dose), and on day 15 (steady state) by 12-lead electrocardiograms (ECGs) performed in triplicate. Pharmacokinetic sampling was also undertaken.

Results: Among 64 evaluable patients, the upper limits of the 2-sided 90 % confidence intervals for the adjusted mean time-matched changes in QTcF interval (corrected for heart rate by Fridericia's method) from baseline to day 1 and 15 (primary ECG endpoint) were well below the regulatory threshold of 10 ms at all times. No relationship between nintedanib exposure and change from baseline in QTcF was seen. Nintedanib was generally well tolerated with no drug-related cardiovascular adverse events.

Conclusion: Nintedanib administered at 200 mg twice daily was not associated with clinically relevant QT prolongation.

Trial registration: ClinicalTrials.gov NCT01024920.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / physiopathology*
  • Electrocardiography / drug effects
  • Female
  • Humans
  • Indoles / blood
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / physiopathology*
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / blood
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use


  • Antineoplastic Agents
  • Indoles
  • Protein Kinase Inhibitors
  • nintedanib

Associated data

  • ClinicalTrials.gov/NCT01024920